By Mike Gene (
Michael Denton and others recently published a paper which can
be viewed as a synthesis of
quote:
Before the
Darwinian revolution many biologists considered organic forms to be determined
by natural law like atoms or crystals and therefore necessary, intrinsic and immutable
features of the world order, which will occur throughout the cosmos wherever
there is life. The search for the natural determinants of organic form, the
celebrated ‘‘Laws of Form’’. was seen as one of the major tasks of biology.
After
Denton et al. begin with an interesting historical survey of
pre-Darwinian thinking, where form took priority over function:
quote:
The widespread
belief that organicforms are lawful ‘‘givens of nature’’ explains why it was
that throughout the pre-Darwinian period from the naturphilosophie of the late
18th century, right up to the period just before the publication of the Origin,
although it was universally accepted that organisms exhibited functional adaptations,
for Goethe, Carus Goeffroy and Owen, it was always form which was of primary
concern. Form came .first and function was viewed as a secondary and derived
adaptive feature (Russell, 1916; Richards, 1992).
Denton et al. explain the decline of this thinking as follows:
quote:
The Platonic
biology of the pre-Darwinian era with its emphasis on evolution by natural law
and its conception of a rational order underlying the diversity of life,
represented a grand scientific vision, whose heroic goal was nothing less than
the unification of biology and physics. It collapsed primarily because it
failed to identify the elusive laws of form which might have provided a
rational account of organic form and explained how the evolution of the basic
invariant forms or types, from cell forms to the body plans of the major phyla,
and deep homologies such as the pentadactyl limb, might have come about as a
result of natural law. That they had no convincing explanation was explicitly
conceded by Owen (1849) in the final paragraph of ‘‘On the Nature of Limbs’’:
‘‘To what natural laws or secondary causes the succession and progression of
such organic phenomena may have been committed we as yet are ignorant.’’
The authors also note:
quote:
Of course no
serious biologist doubts that some biological forms may be given by natural law
and arise spontaneously out of the intrinsic self-organizing properties of
their constituents and may not need any genetic program for their
specification. The spherical form of the cell and the .at form of the cell
membrane are two well known examples. Other more complex examples cited by
Waddington (1962) are the various cytoplasmic structures made up of multiple
layers of membranes such as the grana and intergrana regions of chloroplasts, the
hexagonal arrangement of the rhabdomeres in the eyes of insects and the many
forms described by Thompson (1942) in Growth and Form, including radiolarian
skeletons, the shapes of mollusk shells, the curved shape of animal horns. But
on the whole, natural law is considered to play a very trivial role in the
generation of biological form and particularly in the generation of complex
seemingly asymmetric biological forms such as protein folds, cell forms, body
plans, etc.
Denton et al. then argue that protein folds represent a genuine
example where the pre-darwinian thinking has been validated. Let me quote their
argument at length:
quote:
The protein
folds are the basic building blocks of proteins and therefore of the cell and
indeed of all life on earth. Each is a polymer between 80 and 200 amino acids
long consisting of from about 1000 to 3000 atoms folded up into a complex
intricate three-dimensional shape. Most folds exhibit a hierarchical structure
composed of basic secondary structural elements such as a helices and b sheet
conformations which are often arranged into more complex motifs which are in
turn combined together to make up the native conformation of the fold.
It is important at this stage to note that the great majority of functional proteins
in the cell consist of two or more basic folds linked together into multidomain
or multifold complexes. In this paper we are considering only the fundamental
nature and evolutionary origin of the folds and not of the higher order
adaptive structures into which they are combined. These higher order complexes
resemble, ‘‘Lego-like’’-,contingent assemblages put together by natural
selection for various biological functions during the course of evolution by
gene duplication and fusion (Brandon & Tooze, 1999).
Despite these early successes the lack of any apparent regularity in protein
structures, and the great dissimilarity among those that had been determined,
provided no basis for a rational classification (Ptitsyn & Finkelstein,
1980; Richardson, 1981). The picture was still in those early days compatible
with the Lego model, that the folds in living organisms on earth might be
individual members of a near infinite set of contingent material assemblages
put together by natural selection over millions of years of evolution. It was
only during the 1970s, as the number of 3D structures began to grow
significantly, that it first became apparent that there might not be an
unlimited number of protein folds, that the folds might not belong to a
potentially infinite set of artifactual Lego-like constructs. On the contrary,
it became increasingly obvious as more structures were determined that the
protein folds could be classified into a .finite number of distinct structural
families containing a number of related but variant forms, i.e. that the
classification system of fold structures was typological (Ptitsyn &
Finkelstein, 1980; Richardson, 1981; Orengo et al., 1997). This was an
important finding as the very fact that protein folds can be grouped in such a
way was itself significant, for it provided the .first line of evidence that
the folds might be natural forms determined by physical law.
It also became apparent that the 3D structures of individual folds were
essentially invariant, some such as the Globin fold and the Rossman fold for
example, having remained essentially unchanged for thousands of millions of
years. Both their invariance and the typological classification schemes into
which they could be grouped argued for their being a .finite set of ‘‘real
timeless structures’’ determined by physics rather than being mutable
‘‘Lego-like’’ aggregates of amino acids determined by selection.
Consideration of the various physical constraints which restrict the folded
spatial arrangements of linear polymers of amino acids, the laws of fold form,
suggests that the total number of permissible folds is bound to be restricted
to a very small number. One recent estimate based on possible arrangements of
typical structural elements gave a maximum of 4000 folds (Lingard & Bohr,
1996). Based on similar considerations, the authors of another recent paper
suggested that the maximum is likely to be no more than a few thousand (Chothia
et al., 1997). A different type of estimate based on the rate of discovery of
new folds, rather than permissible spatial arrangements, suggests that the
total number of folds utilized by organisms on earth might not be more than
1000 (Chothia, 1993). In many recent reports the total number of different
folds is often cited to be somewhat less than 1000 (Holm & Sander, 1996;
Orengo et al., 1997; Zhang & DeLisi, 1999; Holm & Sander, 1999).
Whatever the actual figure, the fact that the total number of folds represents
a tiny stable fraction of all possible polypeptide conformations, determined by
the laws of physics, reinforces further the notion that the folds like atoms,
represent a .finite set of allowable physical structures which would recur
throughout the cosmos wherever there is carbon-based life utilizing the same 20
amino acids.
This would seem to be a very important point. If there are only
a few thousand possible protein folds, it strongly suggests that protein folds
are not high information structures. This has very significant implications for
our reconstruction of evolutionary history. Denton et al. don't fully draw this
out (in my opinion), but it is hinted at here:
quote:
Further
evidences consistent with the Platonic conception that the protein folds
represent a set of lawful immutable natural forms, ‘‘primary givens of physics,’’
are those many cases where protein functions are clearly secondary adaptations
of a primary, immutable form (Gerlt & Babbitt, 2001). This is spectacularly
true in the case of some of the more common folds also known as superfolds
(Orengo et al., 1994; Gerlt & Babbitt, 2001). In the case of one superfold
the so-called triosephosphate isomerase (TIM) barrel, an eight-stranded
alpha/beta bundle (see Fig. 1), essentially the same fold, has been secondarily
modified for many completely unrelated enzymic functions occurring in such
diverse enzymes as triosephosphate isomerase, enolase and glycolate oxidase
(Orengo et al., 1994). Another example, where a basic fold has been secondarily
modified for various biochemical functions, in this case closely related functions,
is the various elegant functional adaptations to oxygen uptake and carriage
exhibited by the globin fold in myoglobin and the various vertebrate
hemoglobins. The fact that in many cases where the same fold is adapted to
different functions, no trace of homology can be detected in the amino acid
sequences, suggesting multiple separate discoveries of the same basic structure
during the course of evolution (Orengo et al., 1994; Brandon & Tooze,
1999), further reinforces the conclusion that the folds are a .finite set of
ahistoric physical forms.
Let me
expand on this slightly. If there are only a few thousands protein folds, then
our degree of confidence about homology is greatly weakened if the main pillar
of this inference is based on structural similarity. That is, if we were
dealing with a nearly-infinite number of potential protein folds, then the fact
that two proteins share folds would be strongly suggestive of common descent.
But if the number of structures is quite limited, then an origin through
convergence, or common design, is equally plausible. This is quite significant
in our post-genomic age , given that biologists seem to be relying more and
more on structural similarity to infer 'homology.'
For example, let's assume there are only about 1000 different protein folds.
Let's now imagine that an intelligent designer sought to seed this planet with
microbial life forms containing proteins whose average number of domains was
three. This would mean that our designer could only design about 300-350
proteins before he/she would have to reuse a fold. Since we would not be able
to design a heterogeneous pool of bacteria from such a limited number of
proteins, the design had to reuse protein folds. From the design perspective, the mere sharing
of protein folds is not evidence of homology.
1. Michael J. Denton, Craig J. Marshall and Michael Legge. The Protein Folds as
Platonic Forms: New Support for the Pre-Darwinian Conception of Evolution by
Natural Law. J. Theor. Biol. (2002)
219, 325–342